Heart disease, including myocardial infarction, is a leading cause of death and impaired activity in human beings, particularly in the western world. Ischemic heart disease is the major form of heart failure. A common symptom of cardiac ischemia is chest pain that may lead to heart attack (acute myocardial infarction or AMI) and sudden death.
Myocardial ischemic disorders occur when blood flow in the heart is restricted (ischemia) and/or when the oxygen supply to heart muscle is compromised hypoxia) and the heart's demand for oxygen is not met. Ischemia and hypoxia can be transient and reversible, but can also lead to a heart attack. During such an attack, cardiac tissue is damaged and the heart cells become permeabilized, releasing a portion of their contents to the surrounding environment, including cardiac enzymes and other biochemical markers. These cellular markers, such as creatine kinase (CK), lactic acid dehydrogenase (LDH) and creatine kinase-MB (CKMB) and troponin (I and T) and myoglobin mass levels become detectable in the blood of the patient. The use of these markers and new forms of treatment has increased the survival rate of patients having a heart attack. This factor combined with the increased life expectancy has led to an increase in the prevalence of congestive heart failure (CHF).
CHF causes significant morbidity and mortality, and the health care expenditure for this disease is substantial. The need exists for better diagnostic and prognostic methods for this disease. Recently, assays for B-type natriuretic peptide (BNP) which is secreted by the ventricles in response to ventricular expansion and pressure overload resulting in an elevation of the plasma concentration of BNP have been used in the diagnosis of CHF. BNP levels have been found to increase in proportion to the degree of left ventricular dysfunction and the severity of CHF symptoms and monitoring the levels of circulating BNP has been used to monitor the effectiveness of therapy. Significant decreases in BNP levels correlate with a longer interval between admissions. Thus, BNP monitoring allows therapy to be tailored to maximize the desired effects in an individual patient. Levels of BNP precursor molecules such as the N-terminal proBNP (NT-proBNP), which is released when BNP is cleaved from its precursor, a 108 amino acid molecule, referred to as “pre pro BNP) have also been measured in assays to diagnose CHF, particularly when the patient's therapy includes being treated which a synthetic BNP molecule.
The inability to determine when a patient's CHF is worsening (before a patient gains several pounds in weight and/or edema is greatly increased) until the patient has a doctor's appointment or requires hospitalization will result in a delay of treatment. While in vitro diagnostic assays measuring BNP levels are now in use, these assessments are point-in-time assessments that do not provide the clinician a complete profile of a patient's changing status. Moreover, required changes to the patient's therapy will be delayed.
A recent development in in vitro assays is the use of biosensors as a substrate for the assay. Biosensors are electronic devices that produce electronic signals as the result of biological interactions. Biosensors are commonly divided into two groups. Catalytic sensors that use enzymes, microorganisms, or whole cells to catalyze a biological interaction with a target substance. Affinity systems use antibodies, receptors, nucleic acids, or other members of a binding pair to bind with a target substance, which is typically the other member of the binding pair. Biosensors may be used with a blood sample to determine the presence of an analyte of interest without the need for sample preparation and/or separation steps typically required for the automated immunoassay systems.
Implantable electrochemical biosensors have recently become an important tool for analyzing and quantifying the chemical composition of a patient's blood. For example, glucose sensors are generally employed to measure blood glucose levels in patients having diabetes. Such biosensors are described in U.S. Published Application No. 2002/0120186, the teachings of which are incorporated herein by reference.
It would be desirable to have implantable biosensors for use in in vivo detection and monitoring of biologically relevant markers in the diagnosis and treatment of cardiovascular diseases, including heart failure and myocardial infarction.